This phase II trial tests the effect of autologous tumor infiltrating lymphocytes (TILs) in combination with interleukin-2 (aldesleukin) in treating patients with gastrointestinal stromal tumors (GIST) that has spread to nearby tissue or lymph nodes (locally advanced), that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Autologous TILs are made using the patient's own tumor cells collected from a previous surgery. Lymphocytes (a type of white blood cell) are a part of the immune system that helps the body fight infections. Lymphocytes are found in tumor tissue cells because they are working to attack the tumor. The cells from the tumor are grown in a lab to create more immune cells (lymphocytes). This may help the immune system find and destroy any remaining tumor cells. Aldesleukin is a form of interleukin-2, a cytokine made by leukocytes, that is made in the laboratory. Aldesleukin may help white blood cells and T cells regulate the immune response. Chemotherapy, such as cyclophosphamide and fludarabine, are given before receiving TIL to help kill tumor cells in the body and helps make room for the treatment. Colony-stimulating factors, such as filgrastim, may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Giving autologous TILs in combination with aldesleukin may be safe, tolerable, and/or effective in treating patients with locally advanced, recurrent or metastatic GIST.
PRIMARY OBJECTIVE: I. To evaluate the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous TIL and high-dose aldesleukin in patients with locally advanced, recurrent, or metastatic gastrointestinal stromal tumor (GIST) using the objective response rate (ORR). SECONDARY OBJECTIVES: I. To further evaluate the efficacy of this therapy using complete response (CR) rate, duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). II. To characterize the safety profile of this therapy in patients with locally advanced, recurrent, or metastatic gastrointestinal stromal tumors (GIST). OUTLINE: Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -8 and -7, fludarabine IV over 30 minutes on days -6 to -2 and TIL IV over 20-30 minutes on day 0 in the absence of disease progression or unacceptable toxicity. Starting within 24 hours of TIL infusion, patients receive aldesleukin IV over 15 minutes every 8 hours for up to 6 doses on days 0-3 in the absence of disease progression or unacceptable toxicity. Starting on day 1 or day 2, patients may receive filgrastim subcutaneously (SC) until neutrophil count \> 1 x 10\^9/L for 3 consecutive days or \> 5 x 10\^9/L. Patients with stable disease, partial response or recurrence may receive a second course of treatment. Patients also undergo chest x-ray at screening and urine and blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET) throughout the study. Additionally, patients may also undergo echocardiography or multigated acquisition scan (MUGA) at screening and may also undergo a second surgery to collect cells on study. After completion of study treatment, patients are followed up at 4-6 weeks, 12 weeks, every 3 months for 3 visits, then every 6 months up to month 24.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
59
Given IV
Undergo urine and blood sample collection
Undergo chest x-ray
Undergo CT
Given IV
Undergo echocardiography
Given SC
Given IV
Undergo MRI
Undergo MUGA
Undergo PET
Undergo a second surgery
Given IV
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Objective response rate
Will be estimated by the proportion of patients with a best response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors criteria, with corresponding exact 95% confidence limit being reported.
Time frame: Up to 24 months
CR rate
Will be estimated by the proportion of patients with a best response of complete response (CR) by Response Evaluation Criteria in Solid Tumors criteria
Time frame: Up to 24 months
Duration of response
The distribution among patients achieving CR or PR will be characterized by median and quartiles.
Time frame: Up to 24 months
Disease control rate
Time frame: Up to 24 months
Progression-free survival
Will be estimated by the Kaplan-Meier method. The corresponding median survival times (with 95% confidence limits) will be determined, as will the cumulative percentage of patients remaining progression-free (and the cumulative percentage-alive) at selected time points after initial treatment (e.g., 3, 6,12, 18 months).
Time frame: From the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression), assessed up to 24 months
Overall survival
Will be estimated by the Kaplan-Meier method. The corresponding median survival times (with 95% confidence limits) will be determined, as will the cumulative percentage of patients remaining progression-free (and the cumulative percentage-alive) at selected time points after initial treatment (e.g., 3, 6,12, 18 months).
Time frame: From the initial date of treatment to the recorded date of death, assessed up to 24 months
Incidence of adverse events
Will be described and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The maximum grade of toxicity for each category of interest will be recorded for each patient and the summary results will be tabulated by category and grade.
Time frame: Up to 30 days after treatment
The Ohio State University Comprehensive Cancer Center
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